Tobacco use accounts for 4.9 million deaths annually, with 70% of 2020's 10 million predicted deaths occurring in developing nations. This shocking prediction highlights the need for developing nations to examine patterns and determinants of tobacco use, understand local tobacco use methods, develop effective cessation interventions, and train their own tobacco control scientists. In 2002, with NIH/FIC support, the Syrian Center for Tobacco Studies (SCTS) began this effort in the Eastern Mediterranean Region (EMR). Meanwhile, Syria and other EMR nations ratified the Framework Convention on Tobacco Control (FCTC). This application for continued SCTS support builds on four years of research and training momentum, and prepares Syria and the EMR to meet FCTC obligations. There are four specific aims. First, we seek to understand adolescent tobacco use patterns and determinants: a school-based longitudinal study will examine trends in tobacco use in 4000 Syrian youth. Second, we will examine waterpipe toxicant exposure, dependence, and risk in a laboratory study of 240 waterpipe users placed in three groups based on past-month use frequency. All users will be tested under conditions of 0- and 72-hour abstinence. Particulate matter emissions, a risk for non-users, will also be assessed. Third, we will conduct a randomized clinical trial (multi-site, double blind, placebo-controlled) of a smoking cessation intervention in 250 smokers, while simultaneously studying proximal (e.g., patient) and distal (health care center, staff, policy) factors that can influence the intervention's successful integration within the Syrian public health care system. Fourth, we will continue to build regional tobacco control capacity: our successful program of training Syrian researchers will be maintained, as we also organize and fund three, 1-week, training courses in years 1, 3, and 5 and develop and capitalize on our Research Assistance Matching project. SCTS research and FCTC obligations point to the need for understanding tobacco use determinants, waterpipe use, and cessation efficacy and integration, as well as training of tobacco control researchers across the EMR. This application seeks to build on the past success of the SCTS while helping Syria and the EMR meet their FCTC obligations. Relevance of this research to public health: The proposed work will help understand tobacco use determinants, waterpipe use, and cessation efficacy and integration, which will be instrumental in informing prevention and intervention efforts in Syria and the EMR. Research and training activities proposed will contribute to the building of professional capacity that can aid the successful implementation of the FCTC in the EMR.